Methylphenidate improves the quality of life of children and adolescents with ADHD and difficult-to-treat epilepsies.

OBJECTIVE: Comorbidity between difficult-to-treat epilepsies and ADHD is frequent and impacts negatively on quality of life. The commonly held (yet poorly substantiated) view that stimulants may worsen seizure control has prevented studies from evaluating the impact of such treatment in this population. Our aim was to study the effect of methylphenidate on the quality of life of children and adolescents with difficult-to-treat epilepsies and comorbid ADHD. METHODS: The study was an open-label, noncontrolled trial with intention-to-treat analysis following 30 patients for 6months. Subjects received methylphenidate following 3months of baseline, during which antiepileptic drugs (AEDs) were adjusted and epilepsy, ADHD, and quality-of-life variables were assessed. Multivariate regression analysis identified the main variables correlated with outcome. RESULTS: Only one patient withdrew because of seizure worsening. Following methylphenidate introduction, doses were titrated up to 0.40-0.50mg/kg/day. A marked improvement in quality-of-life scores and a significant reduction in seizure frequency and severity were observed. Female sex, reduction of core ADHD symptoms, and tolerability to adequate doses of methylphenidate were significantly associated with improved quality-of-life scores. CONCLUSION: These preliminary data suggest that methylphenidate treatment is safe and effective in patients with ADHD and difficult-to-treat epilepsies, positively impacting on quality-of-life scores.

The impact of methylphenidate on seizure frequency and severity in children with attention-deficit-hyperactivity disorder and difficult-to-treat epilepsies.

AIM: Difficult-to-treat epilepsies and attention-deficit-hyperactivity disorder (ADHD) often co-occur. Because of concerns about the use of stimulants in children with this comorbidity, the impact of ADHD treatment on seizure frequency and severity is not known. This pilot study evaluated the safety and efficacy of methylphenidate in this population. METHOD: After a 3 month period in which antiepileptic drugs were adjusted, 22 patients recruited from a specialist outpatient clinic for severe epilepsy (16 males, six females; mean age 11 y 2 mo, SD 3 y 2 mo) received methylphenidate for 3 months in an open label, non-controlled trial; four with generalized or multifocal (symptomatic/cryptogenic) epilepsy, one with generalized (idiopathic) epilepsy, 17 with partial (symptomatic/cryptogenic) epilepsy; five with partial seizures only, 17 with primarily or secondarily generalized seizures). Epilepsy, ADHD symptoms, and side effects were assessed using the Swanson, Nolan, and Pelham Questionnaire, the Child Behavior Checklist, the Hague Seizure Severity Scale, and the Side Effects Rating Scale. RESULTS: Methylphenidate significantly improved ADHD. After 3 months of treatment, 73% of patients no longer had clinically significant symptoms. Methylphenidate also reduced seizure severity (9-point median decrease on the Hague Seizure Severity Scale). Seizure frequency increased in four out of 22 patients, but only one patient withdrew from the study for this reason. Most patients experienced no major side effects. INTERPRETATION: These data are among the first showing that low doses of methylphenidate are safe and effective to treat ADHD symptoms in patients with difficult-to-treat epilepsies. Randomized controlled trials are needed to replicate the findings.

Long-term control of epileptic drop attacks with the combination of valproate, lamotrigine, and a benzodiazepine: a 'proof of concept,' open label study.

PURPOSE: Long-term medical management of epileptic drop attacks is usually unsatisfactory and more effective antiepileptic drug (AED) regimens are needed. The present study aimed at providing proof of concept that previously refractory epileptic drop attacks could be significantly and safely controlled by the specific combination of valproate, lamotrigine, and a benzodiazepine. METHODS: An open label trial providing class IV evidence of efficacy, including 32 patients with cryptogenic/symptomatic, generalized or multifocal epilepsies, and refractory drop attacks. Following baseline, the combination under study was introduced and patients followed for 12 months. Frequency of drop attacks was compared at 3-month intervals with that during baseline and correlated with clinical, electroencephalography (EEG), and imaging variables. A list of putative side effects was read to patients and caregivers at each visit. KEY FINDINGS: Four patients were excluded, one due to a Stevens-Johnson syndrome (SJS). Median number of drop attacks decreased 96% between baseline and the fourth trimester of the study (from 50 to 2; p<0,001). Intention-to-treat (ITT) analysis showed that 15 patients (47%) had complete control, 7 (21%) had a 75% and 5 (15%) had a 50-74% reduction in the frequency of falls in the fourth trimester. Twenty-two patients (68%) had side effects, but except for the three excluded because of early rash, caregivers did not consider discontinuation. Mean final dose of valproate was 35.9 mg/kg/day and that of lamotrigine 4.9 mg/kg/day. Twenty patients used clobazam, eight nitrazepam, and the other four clonazepam as the elected benzodiazepine. Outcome did not correlate with clinical, EEG, and imaging variables. SIGNIFICANCE: This open label study suggests that the combination of valproate, lamotrigine, and a benzodiazepine can markedly reduce the frequency of epileptic drop attacks in patients with generalized or multifocal epilepsies. Careful clinical monitoring for early signs of SJS is needed.